Inhibition of interferon signaling by dengue virus

Proc Natl Acad Sci U S A. 2003 Nov 25;100(24):14333-8. doi: 10.1073/pnas.2335168100. Epub 2003 Nov 11.

Abstract

Dengue virus is a worldwide-distributed mosquito-borne flavivirus with a positive strand RNA genome. Its transcribed polyprotein is cleaved by host- and virus-encoded peptidases into 10 proteins, some of which are of unknown function. Although dengue virus-infected cells seem to be resistant to the antiviral action of IFN, the viral products that mediate this resistance are unknown. Therefore, we have analyzed the ability of the 10 dengue virus-encoded proteins to antagonize the IFN response. We found that expression in human A549 cells of the dengue virus nonstructural proteins NS2A, NS4A, or NS4B enhances replication of an IFN-sensitive virus. Moreover, expression of NS4B and, to a lesser extent, of NS2A and NS4A proteins results in down-regulation of IFN-beta-stimulated gene expression. Cells expressing NS4B or infected with dengue virus do not exhibit nuclear signal transducer and activator of transcription (STAT) 1 on treatment with IFN-beta or IFN-gamma, indicating that NS4B might be involved in blocking IFN signaling during dengue virus infections. This protein, encoded by a positive strand RNA virus, is implicated as an IFN-signaling inhibitor.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Line
  • Chick Embryo
  • Chlorocebus aethiops
  • DNA-Binding Proteins / metabolism
  • Dengue Virus / genetics
  • Dengue Virus / immunology
  • Dengue Virus / pathogenicity*
  • Dengue Virus / physiology
  • Humans
  • Interferon Type I / pharmacology
  • Interferon-gamma / pharmacology
  • Interferons / physiology*
  • Phosphorylation
  • Recombinant Proteins
  • STAT1 Transcription Factor
  • Signal Transduction
  • Trans-Activators / metabolism
  • Vero Cells
  • Viral Proteins / genetics
  • Viral Proteins / immunology
  • Viral Proteins / physiology

Substances

  • DNA-Binding Proteins
  • Interferon Type I
  • Recombinant Proteins
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • Trans-Activators
  • Viral Proteins
  • Interferon-gamma
  • Interferons